Coenzyme Q10 Plus NADH Supplementation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Chronic Fatigue Syndrome Clinical Trial

— CONNeCT  

Official title:

Effect of Coenzyme Q10 Plus NADH Supplementation on the Changes in Fatigue Perception, Sleep Disturbances, Autonomic Function and Health-related Quality of Life in CFS/ME - A Randomized, Placebo-controlled, Double-blind Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03186027
• Other study ID #: VITAE 2015
• Status: Completed
• Phase: N/A
• Start date: June 28, 2017
• Est. completion date: September 1, 2021

Study information

• Verified date: September 2022
• Source: Hospital Universitari Vall d'Hebron Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main aim of the study is to examine the effect of oral CoQ10 plus NADH (Reconnect®) supplementation twice daily for 8-weeks on the changes in fatigue perception, sleep disturbances, autonomic dysfunction and HRQoL assessed by patient-reported outcome measures in CFS/ME.

Description:

Chronic Fatigue Syndrome, as known as Myalgic Encephalomyelitis (CFS/ME) is a complex and extremely debilitating chronic condition, with no known cause, no established diagnostic tests, and no universal effective therapy. Its symptoms are mainly unexplained disabling fatigue that lasts for six months or more and that does not improve with rest, worsing with physical and mental activity. It is associated with other concomitant symptoms including muscle pain, post-exertional malaise lasting more than 24h, unrefreshing sleep, autonomic dysfunction and cognitive problems worsing quality of life of sufferers. Previous studies have shown that CFS/ME subjects have a significant decrease in CoQ10 and NADH levels in plasma and peripheral blood mononuclear cells (PBMCs), correlating with symptoms of the condition. Hypothesis: CoQ10 plus NADH administration could be beneficial in the improvement of outcome measures and molecular parameters in CFS/ME individuals. A total of 282 potentially eligible Caucasian CFS/ME subjects who meet both the 1994 Centers for Disease Control and Prevention/Fukuda's definition and 2003 Canadian case criteria for CFS/ME will be initially enrolled in the study. Those patients who don't meet the inclusion criteria will excluded of the study. All participants will be treatment with ReConnect® containing CoQ10 (50 mg) plus NADH (5 mg) vs. placebo twice daily for 8-weeks in term. Scores for fatigue perception, sleep problems, autonomic dysfunction and QoL will be assess by validated questionnaires of Fatigue Impact Scale (FIS-40), Pittsburgh Sleep Quality Index (PSQI), COMPASS-31 and HRV recording device, and HRQoL (36 item Short Form Health survey), respectively. The primary outcome is to evaluate the efficacy of oral CoQ10 plus NADH (Reconnect®) supplementation twice daily for 8-weeks on the changes in fatigue perception, sleep problems, autonomic dysfunction and health-related quality of life assessed by outcome measures in CFS/ME subjects. The secondary outcomes are to examine the effect of oral Reconnect® administration on fatigue perception (assessed by FIS-40), sleep disruption (PSQI), autonomic function (COMPASS-31), Heart Rate Variability (HRV) for measuring R-R intervals by mobile device coupled to the Polar H7 thoracic belt and HRQoL (36-items Short Form Health survey).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 282
• Est. completion date: September 1, 2021
• Est. primary completion date: May 28, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Patients female between 18 and 65 years old.

2. Body Mass Index (BMI) = 30 mg/m²

3. Subjects who met the 1994 Centers for Disease Control and Prevention/Fukuda definition and 2003 Canadian diagnostic criteria for CFS/ME.

4. Patients must be able to participate, understand and complete questionnaires in Spanish language.

5. Patients who give a signed informed consent before initiating the study.

Exclusion Criteria:

1. Patients who do not fulfilled the 1994 Centers for Disease Control and Prevention/Fukuda definition and 2003 Canadian criteria for CFS/ME.

2. Patients who are participating in another clinical trial of the same or different nature in the last 30 days prior to inclusion.

3. Any participants who, in the opinion of the principal investigator, may not be able to follow instructions or make a good treatment compliance.

4. Subjects that don't give signed informed consent to participate in the study.

5. Participants who are receiving any drug or banned substances and is expected that withdrawal of some medications/products not allowed in the study involves a significant problem.

6. Participants who are pregnant and/or breastfeeding,

7. Participants with autoimmune disorder, cancer, endocrine and metabolic disorders, rheumatic conditions, multiple sclerosis, psychosis, major depression, cardiovascular disease, hematological conditions, use of oral anticoagulants, smokers or had a history of substance abuse.

Related Conditions & MeSH terms

• Chronic Fatigue Syndrome
• Fatigue
• Fatigue Syndrome, Chronic
• Syndrome

Intervention

Dietary Supplement:
• Coenzyme Q10 plus NADH
Active arm: Coenzyme Q10 plus NADH CFS/ME patients who will be randomized to measure the effect of oral ReConnect supplementation (CoQ10: 200 mg/day plus NADH 20 mg/day; 4 tablets/day) on changes in the fatigue, sleep problems, autonomic function and HRQoL during 8-weeks in term. Intervention: Reconnect
• phosphoserine plus vitamin C
Placebo arm: phosphoserine plus vitamin C CFS/ME patients who will be randomized to measure the effect of oral Placebo supplementation (phosphoserine and vit C, 4 tablets/day) on changes in the fatigue, sleep problems, autonomic function and HRQoL during 8-weeks in term. Intervention: placebo

Locations

Country	Name	City	State
Spain	Vall d'Hebron University Hospital	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Universitari Vall d'Hebron Research Institute	Vitae Health Innovation

Country where clinical trial is conducted

Spain, 

References & Publications (6)

Alegre J, Rosés JM, Javierre C, Ruiz-Baqués A, Segundo MJ, de Sevilla TF. [Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome]. Rev Clin Esp. 2010 Jun;210(6):284-8. doi: 10.1016/j.rce.2009.09.015. Epub 2010 May 5. Spanish. — View Citation

Castro-Marrero J, Cordero MD, Sáez-Francas N, Jimenez-Gutierrez C, Aguilar-Montilla FJ, Aliste L, Alegre-Martin J. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia? Antioxid Redox Signal. 2013 N — View Citation

Castro-Marrero J, Cordero MD, Segundo MJ, Sáez-Francàs N, Calvo N, Román-Malo L, Aliste L, Fernández de Sevilla T, Alegre J. Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? Antioxid — View Citation

Castro-Marrero J, Sáez-Francàs N, Santillo D, Alegre J. Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome. Br J Pharmacol. 2017 Mar;174(5):345-369. doi: 10.1111/bph.13702. Epub 2017 Feb 1. Review. — View Citation

Castro-Marrero J, Sáez-Francàs N, Segundo MJ, Calvo N, Faro M, Aliste L, Fernández de Sevilla T, Alegre J. Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndro — View Citation

Curriu M, Carrillo J, Massanella M, Rigau J, Alegre J, Puig J, Garcia-Quintana AM, Castro-Marrero J, Negredo E, Clotet B, Cabrera C, Blanco J. Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome. J Trans — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of oral Reconnect ® (CoQ10 plus NADH) supplementation on the changes in core symptoms during 8-weeks in CFS/ME subjects.	Evaluate the effect of oral Reconnect ® supplementation on the changes in fatigue perception measured by the Fatigue Index Scale-40 (40 items) in all study participants. Items Rate: 0 (no fatigue) to 4 (severe fatigue).	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Secondary	Demographic data and clinical parameters	Sex	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Secondary	Age of onset of symptoms	Age at onset of fatigue	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Secondary	Concomitant conditions	Comorbid illnesses associated with ME/CFS	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Secondary	Height will be measured and reported	Height in meters	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Secondary	Weight will be measured and reported	Weight in kilograms	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Secondary	Body Mass Index (BMI)	Height and Weight will be combined to report BMI in kg/m^2	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Secondary	Sleep Quality	Pittsburgh Quality of Sleep Index (18 items) for non-refreshing sleep	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Secondary	Autonomic Function	COMPASS-31 Questionnaire (31-items) to assess autonomic dysfunction	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Secondary	Heart Rate Variability (HRV) recording device	Time domain - NN (normal-to-normal R-R interval), HRV index (total number of all NN/ the height of the histogram of all NN), SDNN (standard deviation of the NN), RMSSD (the root mean square of differences of successive NN), NN50 (number of pairs of adjacent NN intervals differing by more than 50 ms in the entire recording) and pNN50(NN50/total number of all NN). Frequency domain - TP (the variance of NN intervals over the temporal segment), VLF(power in very low frequency range; < 0.04 Hz), LF (Power in low frequency range; 0.04~0.15 Hz), HF(Power in high frequency range; 0.15~0.4 Hz).	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Secondary	Health-Related Quality of Life SF36 survey	Short Form-36 Health Survey (36-items) to measure quality of life of participants.	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)

External Links

•   Vall d'Hebron University Hospital (HUVH)
•   Vall d'Hebron University Hospital Research Institute (VHIR)